Effect of different combinations of initial body temperature and target temperature on neurological outcomes in out-of-hospital cardiac arrest patients treated with targeted temperature management

We hypothesized that different combinations of initial and target temperatures during targeted temperature management (TTM) may be associated with neurological outcomes in out-of-hospital cardiac arrest (OHCA) survivors. Adult patients with OHCA who underwent TTM were enrolled. The study participants were divided into four groups: lower initial body temperature and lower target temperature (Low-Low group), lower initial body temperature and higher target temperature (Low-High group), higher initial body temperature and lower target temperature (High-Low group), and higher initial body temperature and higher target temperature (High-High group). Initial body temperature was dichotomized based on the median value (35.6 ◦C) as a cutoff, and the target temperature was dichotomized with a target temperature of 34 ◦C as a cutoff. The primary outcome was defined as a favorable 28-day neurological outcome. In total, 231 patients were included in the analysis, and 74 (32.0%), 43 (18.6%), 82 (35.5%), and 32 (13.9%) patients were classified into the Low-Low, Low-High, High-Low, and High-High groups, respectively. The proportion of patients with favorable 28-day neurological outcomes differed among the study groups (Low-Low, 14 (18.9%); Low-High, 7 (16.3%); High-Low, 37 (45.1%); High-High, 11 (34.4%); p = 0.001). In the multivariable analysis, the Low-High group was independently associated with a less favorable 28-day neurological outcome compared to the High-Low group (adjusted odds ratio, 0.22; 95% confidence interval, 0.06–0.91; p = 0.036). In conclusion, higher initial body temperature and lower target temperature during TTM were independently associated with a more favorable 28-day neurological outcome compared to the lower initial body temperature and higher target temperature in patients resuscitated from OHCA of medical etiology.

Cardiac arrest; Targeted temperature management; Hyperthermia; Hypothermia

[1] Berdowski J, Berg RA, Tijssen JG, Koster RW. Global incidences of out-of-hospital cardiac arrest and survival rates: systematic review of 67 prospective studies. Resuscitation. 2010; 81: 1479–1487.

[2] Kim JY, Hwang SO, Shin SD, Yang HJ, Chung SP, Lee SW, et al. Korean Cardiac Arrest Research Consortium (KoCARC): rationale, development, and implementation. Clinical and Experimental Emergency Medicine. 2018; 5: 165–176.

[3] Geocadin RG, Callaway CW, Fink EL, Golan E, Greer DM, Ko NU, et al. Standards for studies of neurological prognostication in comatose survivors of cardiac arrest: a scientific statement from the american heart association. Circulation. 2019; 140: e517–e542.

[4] Merchant RM, Becker LB, Abella BS, Asch DA, Groeneveld PW. Cost-effectiveness of therapeutic hypothermia after cardiac arrest. Circulation. 2009; 2: 421–428.

[5] Kida K, Ichinose F. Preventing ischemic brain injury after sudden cardiac arrest using no inhalation. Critical Care. 2014; 18: 212.

[6] Nolan JP, Sandroni C, Böttiger BW, Cariou A, Cronberg T, Friberg H, et al. European resuscitation council and European society of intensive care medicine guidelines 2021: post-resuscitation care. Intensive Care Medicine. 2021; 47: 369–421.

[7] Panchal AR, Bartos JA, Cabanas JG, Donnino MW, Drennan IR, Hirsch KG, et al. Part 3: adult basic and advanced life support: 2020 American heart association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2020; 142: S366–S468.

[8] Langhelle A, Tyvold SS, Lexow K, Hapnes SA, Sunde K, Steen PA. In-hospital factors associated with improved outcome after out-of-hospital cardiac arrest. a comparison between four regions in Norway. Resuscitation. 2003; 56: 247–263.

[9] Nolan JP, Laver SR, Welch CA, Harrison DA, Gupta V, Rowan K. Outcome following admission to UK intensive care units after cardiac arrest: a secondary analysis of the ICNARC case mix programme database. Anaesthesia. 2007; 62: 1207–1216.

[10] Suffoletto B, Peberdy MA, van der Hoek T, Callaway C. Body temperature changes are associated with outcomes following in-hospital cardiac arrest and return of spontaneous circulation. Resuscitation. 2009; 80: 1365–1370.

[11] Kil HY, Zhang J, Piantadosi CA. Brain temperature alters hydroxyl radical production during cerebral ischemia/reperfusion in rats. Journal of Cerebral Blood Flow & Metabolism. 1996; 16: 100–106.

[12] Miao YF, Wu H, Yang SF, Dai J, Qiu YM, Tao ZY, et al. 5′-adenosine monophosphate-induced hypothermia attenuates brain is-chemia/reperfusion injury in a rat model by inhibiting the inflammatory response. Mediators of Inflammation. 2015; 2015: 520745.

[13] Cao J, Xu J, Li W, Liu J. Influence of selective brain cooling on the expression of ICAM-1 mRNA and infiltration of PMNLs and monocytes/macrophages in rats suffering from global brain is-chemia/reperfusion injury. Biosci Trends. 2008; 2: 241–244.

[14] Leary M, Grossestreuer AV, Iannacone S, Gonzalez M, Shofer FS, Povey C, et al. Pyrexia and neurologic outcomes after therapeutic hypothermia for cardiac arrest. Resuscitation. 2013; 84: 1056–1061.

[15] Cocchi MN, Boone MD, Giberson B, Giberson T, Farrell E, Salciccioli JD, et al. Fever after rewarming: incidence of pyrexia in postcardiac arrest patients who have undergone mild therapeutic hypothermia. Journal of Intensive Care Medicine. 2014; 29: 365–369.

[16] Bro-Jeppesen J, Hassager C, Wanscher M, Søholm H, Thomsen JH, Lippert FK, et al. Post-hypothermia fever is associated with increased mortality after out-of-hospital cardiac arrest. Resuscitation. 2013; 84: 1734–1740.

[17] Gebhardt K, Guyette FX, Doshi AA, Callaway CW, Rittenberger JC. Prevalence and effect of fever on outcome following resuscitation from cardiac arrest. Resuscitation. 2013; 84: 1062–1067.

[18] Peberdy MA, Callaway CW, Neumar RW, Geocadin RG, Zimmerman JL, Donnino M, et al. Part 9: post-cardiac arrest care. Circulation. 2010; 122: S768–S786.

[19] Callaway CW, Donnino MW, Fink EL, Geocadin RG, Golan E, Kern KB, et al. Part 8: post-cardiac arrest care: 2015 American heart association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2015; 132: S465–S482.

[20] Kwon WY, Jung YS, Suh GJ, Kim T, Kwak H, Kim T, et al. Regional cerebral oxygen saturation in cardiac arrest survivors undergoing targeted temperature management 36 ◦C versus 33 ◦C: a randomized clinical trial. Resuscitation. 2021; 167: 362–371.

[21] Zeiner A, Holzer M, Sterz F, Schörkhuber W, Eisenburger P, Havel C, et al. Hyperthermia after cardiac arrest is associated with an unfavorable neurologic outcome. Archives of Internal Medicine. 2001; 161: 2007–2012.

[22] Sekhon MS, Ainslie PN, Griesdale DE. Clinical pathophysiology of hypoxic ischemic brain injury after cardiac arrest: a “two-hit” model. Critical Care. 2017; 21: 90.

[23] Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager Y, et al. Targeted temperature management at 33 ◦C versus 36 ◦C after cardiac arrest. The New England Journal Medicine. 2013; 369: 2197–2206.

[24] Lascarrou JB, Merdji H, Le Gouge A, Colin G, Grillet G, Girardie P, et al. Targeted temperature management for cardiac arrest with nonshockable rhythm. New England Journal of Medicine. 2019; 381: 2327–2337.

[25] Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. New England Journal of Medicine. 2002; 346: 557–563.